POS0412 INTRA-ARTICULAR INJECTION OF STIGMASTEROL LOADED NANOPARTICLES IS EFFECTIVE IN INHIBITING JOINTS DESTRUCTION IN OSTEOARTHRITIS RAT MODEL
Authors: J. H. Jung, B. Y. Kim, S. W. Nam
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Stigmasterol is the most abundant plant sterols and its chemical structure is very close to cholesterol. Stigmaterol inhibits pro-inflammatory and matrix degradative mediators typically involved in cartilage degradation through inhibition of the nuclear factor kappa-B (NF-κB) pathway and attenuates chondrocyte injury induced by interleukin-1β (IL-1β). Mesoporous silica nanomaterials (MSNs) have been proven to be promising nanoparticles due to their superior loading capability, multitudinous functionalization, and biocompatibility. Since osteoarthritis (OA) is mainly developed in weight bearing or overused joints, the locally sustained therapy using nanoparticles is effective for targeting inflammatory component of OA. <h3>Objectives</h3> This study aimed to investigate the effects of intra-articular injection of rebamipide loaded MSNs in OA rat model. <h3>Methods</h3> We modified the surface of MSNs using tannic acid and anchor the stigmasterol that allow the sustained release of stigmasterol from nanoparticles. In vitro, lipopolysaccharide induced RAW cell were used to investigate the cytotoxicity and anti-inflammatory effect of stigmasterol-loaded MSNs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into five groups, consisting of healthy control rats and rats injected with MIA alone or in combination with MSNs, stigmasterol (10 µg)/MSNs, stigmasterol (50 µg)/MSNs. The levels of IL-6, matrix metalloproteinase-3 (MMP-3), and tumor necrosis factor- α (TNF-α) measured periodically and the micro-computed tomography (CT) and histological examination was performed at eight week. <h3>Results</h3> In vitro, stigmasterol/MSNs dose-dependently suppressed the levels of pro-inflammatory mediators, including IL-6, MMP-3 and TNF-α. In vivo, the levels of pro-inflammatory components most markedly decreased in the intra-articularly injected stigmasterol (50 µg)/MSNs group compared to other groups. Micro-CT images and histological evaluations showed that the intra-articular injection of stigmasterol/MSNs also inhibited cartilage degeneration dose-dependently. <h3>Conclusion</h3> Using a chemically induced rat model of OA, intra-articular delivery of stigmasterol was associated with decreased local and systemic inflammatory response decreased joint degradation and arthritic progression. <h3>References</h3> [1]Gabay O, Sanchez C, Salvat C, et al. Stigmasterol: a phytosterol with potential anti-osteoarthritic properties. Osteoarthritis Cartilage. 2010; 18: 106-116. [2]Chen WP, Yu C, Hu PF, et al. Stigmasterol blocks cartilage degradation in rabbit model of osteoarthritis. Acta Biochim Pol. 2012; 59: 537-541. [3]Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility, and drug delivery. Adv Mater. 2012; 24: 1504-1534. [4]Kuyinu EL, Narayanan G, Nair LS, et al. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res. 2016; 11: 19. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.